阿托伐他汀钙关键中间体2-[2-(4-氟苯基)-2-羰基-1-苯基]-4-甲基-3-羰基-戊酸甲酯的合成

Synthesis of Atorvastatin Calcium Key Intermediate 2-(2-(4-Fluorophenyl)-2-carbonyl-1-phenyl)-4-methyl-3-carbonyl-pentanoic acid methyl ester

以苯乙酰氯(Ⅱ)和氟苯(Ⅲ)为起始原料,经Friedel-Crafts酰化反应合成1-(4-氟苯基)-2-苯乙酮(Ⅳ),再与溴素发生取代反应得到2-溴-1-(4-氟苯基)-2-苯乙酮(Ⅴ),最后与异丁酰乙酸甲酯(Ⅵ)反应得到阿托伐他汀钙关键中间体2-[2-(4-氟苯基)-2-羰基-1-苯基]-4-甲基-3-羰基-戊酸甲酯(Ⅰ)。经^(1)HNMR鉴定,各中间体及产物与目标物均一致。该工艺合成步骤较少,后处理简单,有良好的工业化应用前景。

Taking phenylacetyl chloride(Ⅱ)and fluorobenzene(Ⅲ)as starting materials,we firstly synthesized 1-(4-fluorophenyl)-2-acetophenone(Ⅳ)by Friedel-Crafts acylation reaction.Then,we synthesized 2-bromo-1-(4-fluorophenyl)-2-acetophenone(Ⅴ)by the reaction of the compoundⅣwith bromine.Finally,we synthesized Atorvastatin calcium key intermediate 2-(2-(4-fluorophenyl)-2-carbonyl-1-phenyl)-4-methyl-3-carbonyl-pentanoic acid methyl ester(Ⅰ)by the reaction of the compoundⅤwith butyl acyl methyl acetate(Ⅵ).The intermediates and products are consistent with the target compounds by ^(1)HNMR identification.The process has the characteristics of few synthetic steps and simple post-treatment,which has a good industrial application prospect.